P31 SINGLE-AGENT BELANTAMAB MAFODOTIN IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA: FINAL ANALYSIS OF THE DREAMM-2 TRIAL
Authors: A. Nooka, A. Cohen, H. Lee, A. Badros, A. Suvannasankha, N. Callander, A. Abdallah, S. Trudel, A. Chari, E. Libby, M. Chaudhry, M. Hultcrantz, K.M. Kortüm, P. Richardson, R. Popat, D. Sborov, S. Hakim, E. Lewis, B. Bhushan, B. Gorsh, I. Gupta, J. Opalinska, S. Lonial
Journal: HemaSphere (2023)

Objectives: Belantamab mafodotin (belamaf)—a first-in-class, antibody-drug conjugate targeting B-cell maturation antigen—demonstrated deep and durable responses with a manageable safety profile in previous analyses of the pivotal DREAMM-2 study in patients with relapsed/refractory myeloma (RRMM). Here, we present final efficacy and safety data from DREAMM-2. Methods: DREAMM-2 (NCT03525678) is a Phase 2, open-label study of single-agent belamaf (2.5 or 3.4 mg/kg every 3 weeks) in patients with triple-refractory RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 monoclonal antibody. The primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life (HRQoL). Results: As of 31 March 2022, median follow-up was 12.48 and 13.77 months for patients randomised to belamaf 2.5 mg/kg (N=97) and 3.4 mg/kg (N=99), respectively (Table). ORR in the 2.5 and 3.4 mg/kg cohorts was 32% and 35%, respectively; 19% and 24% of patients (58% and 69% of responders, respectively) achieved very good partial response (VGPR) or better. Median time to response was 1.5 and 1.4 months in the 2.5 and 3.4 mg/kg cohorts, respectively. The minimal residual disease negativity rate of patients with ≥VGPR was 36% and 23%, and median duration of response was 12.5 and 6.2 months in the 2.5 and 3.4 mg/kg cohorts, respectively. Median PFS was 2.8 and 3.9 months, and median OS was 15.3 and 14.0 months in the 2.5 and 3.4 mg/kg cohorts, respectively. In patients who achieved ≥VGPR, median PFS was 14.0 and 16.8 months, and OS was 30.7 and 35.5 months in the 2.5 and 3.4 mg/kg cohorts, respectively. The three most common Grade ≥3 adverse events (AEs) were keratopathy, anemia, and thrombocytopenia (Table). Incidences of AE-related dose reductions, delays and permanent discontinuations were 36% and 44%, 54% and 62%, and 9% and 5% in the 2.5 and 3.4 mg/kg cohorts, respectively. Discontinuation due to ocular events was rare (3% in both cohorts). The most commonly reported ocular events in the 2.5 mg/kg cohort included keratopathy (71%), blurred vision (23%), BCVA reduced to 20/50 (21%) and dry eye (15%). BCVA reductions and blurred vision were transient; ≤86% of patients experiencing these events had resolution by completion of follow-up. No permanent complete vision loss occurred. Despite changes in BCVA and blurred vision, European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire data suggest that overall global health status/HRQoL, physical and role functioning, and overall disease symptoms were maintained or improved during treatment. Table. - Key efficacy and safety outcomes of the DREAMM-2 final analysis Outcome Belamaf 2.5 mg/kg Q3W (N=97; N=95 for safety analyses) Belamaf 3.4 mg/kg Q3W (N=99) Median time on therapy, months (range) 2.1 (0.5–41.0) 2.8 (0.5–42.8) Median follow-up, months (range) 12.48 (0.1–40.4) 13.77 (0.1–42.8) ORR, % (97.5% CI) 32 (21.7–43.6) 35 (24.8–47.0) ≥VGPR, % 19 24 MRD-negativity rate in ≥VGPR, % (95% CI)* 36 (12.8–64.9) 23 (5.0–53.8) Duration of response, months (95% CI) 12.5 (4.2–19.3) 6.2 (4.8–18.7) Median PFS, months (95% CI) 2.8 (1.6–3.6) 3.9 (2.0–5.8) Median PFS in ≥VGPR, months (95% CI) 14.0 (9.7–NR) 16.8 (7.7–NR) Median OS, months (95% CI) 15.3 (9.9–18.9) 14.0 (10.0–18.1) Median OS in ≥VGPR, months (95% CI)† 30.7 (19.7–37.9) 35.5 (14.1–NR) AE-related dose reductions, % 36 44 AE-related dose delays, % 54 62 AE-related permanent discontinuations, % 9 5 Permanent discontinuation due to ocular events, % 3 3 Grade ≥3 AEs, % 84 83 Keratopathy, % 29 25 Anemia, % 21 28 Thrombocytopenia, % 19 29 *MRD was measured by next generation sequencing with a threshold of 10−5.†Median OS in ≥VGPR patients was a post-hoc analysis.AE, adverse event; CI, confidence interval; DREAMM, DRiving Excellence in Approaches to Multiple Myeloma; MRD, minimal residual disease; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; Q3W, every 3 weeks; VGPR, very good partial response. Conclusions: This final analysis of DREAMM-2 confirms earlier reports that single-agent belamaf (2.5 and 3.4 mg/kg) results in rapid, deep, durable and clinically meaningful responses, with a manageable safety profile in patients with RRMM. No new safety signals were observed. Dose modification remained effective in resolving ocular events, and HRQoL was maintained or improved.